The following discussion of the background of the invention is merely provided to aid the reader in understanding the invention and is not admitted to describe or constitute prior art to the present invention.
Fluoroquinolones are antibiotics used to treat infections caused by microorganisms. Fluoroquinolones have the basic structure shown below:
wherein R1, R2, R3, and R4 can be a variety of functional groups and X can be carbon or a variety of heteroatoms either of which may be substituted or unsubstituted.
Fluoroquinolones were first developed in the early 1960s. The first fluoroquinolone, nalidixic acid, was approved by the FDA in 1963 for the treatment of urinary tract infections. Nalidixic acid is rapidly absorbed after oral administration and is excreted into the urine in bactericidal concentrations. Nalidixic acid, however, has several limitations that prevents its use in other types of infections. Specifically, nalidixic acid has a narrow spectrum of activity and microorganisms easily developed resistance to the drug. The development of other fluoroquinolones by chemically altering the basic structure of nalidixic acid, however, has led to improved fluoroquinolone that are more effective against resistant bacteria and effective against a broader range of bacteria.
Representative fluoroquinolones include, but are not limited to, those described in BE 870,576, U.S. Pat. No. 4,448,962, DE 3,142,854, EP 047,005, EP 206,283, BE 887,574, EP 221,463, EP 140,116, EP 131,839, EP 154,780, EP 078,362, EP 310,849, EP 520,240, U.S. Pat. No. 4,499,091, U.S. Pat. No. 4,704,459, U.S. Pat. No. 4,795,751, U.S. Pat. No. 4,668,784, and U.S. Pat. No. 5,532,239.
The fluoroquinolone class of antibiotics are a powerful tool in combating bacterial infections. Fluoroquinolones have been used extensively to treat respiratory tract infections (including for example, bronchitis, pneumonia, tuberculosis), urinary tract infections, diarrhea, postoperative-wound infections, bone and joint infections, skin infections, inflammation of the prostate, ear infections, various sexually transmitted diseases, various infections that affect people with AIDS, and other conditions, in animals and humans. Fluoroquinolone are active against a wide spectrum of gram-positive and gram-negative bacteria. For example, various fluoroquinolones have been found to be effective against Staphylococcus aureus, Streptococcus pneumoniae, coagulese-negative staphylococci, Streptococcus pyogenes, Staphylococcus epidermis, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Proteus vulgaris, Providencia stuartii, Morganella morganii, Citrobacter diversus, Citrobacter freundii, Haemophilus influenzae, and Neisseria gonorrhea, and other organisms. Indeed, the mounting resistance of Staphylococcus aureus to both penicillin and erythromycin has made the fluoroquinolone antibiotics a viable alternative for the treatment of skin diseases.
The mode of action of fluoroquinolones is to target DNA gyrase in the bacteria and interfere with bacterial replication.
Fluoroquinolones can be administered orally, topically, or parenterally.
U.S. Pat. No. 5,476,854 describes the oral, intravenous, and transdermal use of lomefloxacin to treat urinary tract infections, upper respiratory tract infections, sexually-transmitted infections, opthalmological infections, and intestinal infections.
U.S. Pat. No. 6,017,912 discloses a method of topically treating bacterial infections of the skin caused by susceptible organisms that comprises administering to an individual a composition of a fluoroquinolone antibiotic in a vehicle containing acetone and alcohol, applied directly to the affected areas of the human skin.
U.S. Pat. No. 5,912,255 discloses a pharmaceutical composition comprising a fluoroquinolone and benzoyl peroxide in a vehicle. The compositions are useful for the topical treatment of a variety of skin conditions.
U.S. Pat. No. 5,756,506 discloses a method of treating animals with fluoroquinolones by administering to the animal a single high dose of the fluoroquinolone to replace multiple lower doses.
U.S. Pat. No. 5,532,239 discloses treating nephrotic syndromes with fluoroquinolone derivatives.
U.S. Pat. No. 6,887,487 discloses compositions comprising a salt of a pharmacologically active compound and a lipophilic counterion and a pharmaceutically acceptable water soluble solvent combined together to form an injectable composition. The patent also discloses methods of treating a mammal with the disclosed compositions.
U.S. Pat. No. 5,484,785 discloses 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-quinoline-3-carboxylic acid 5-oxotetrahydrofuran-2-carboxylate or 2-hydroxyglutarate and processes for making the same.
U.S. published application no. 2005/0049210 discloses composition for the administration of a pharmacologically active compound to a mammal comprising: a salt of the pharmacologically active compound with a lipophilic counterion; and a pharmaceutically acceptable, water immiscible solvent; combined together to form a composition that releases the active compound over time when administered to the mammal. The published application also discloses methods of treating a mammal with the disclosed compositions.
Solid oral pharmaceutical compositions, such as tablets and capsules, can be difficult for some individuals to swallow. For example, pediatric patients often find it difficult to swallow solid oral pharmaceutical compositions. Furthermore, solid oral pharmaceutical compositions can be difficult to administer to animals, such as cats. Thus, in many instances, liquid oral pharmaceutical compositions, such as solutions and suspensions, are desirable because they are easier to administer. Fluoroquinolones, however, are difficult to dissolve in aqueous liquids. Accordingly, there is a need in the art for new liquid fluoroquinolone compositions that can be more easily administered to animals.
The difficulty in dissolving fluoroquinolones in aqueous solutions also makes it difficult to develop fluoroquinolone compositions that are suitable for injection.
Citation of any reference in this section of this application is not to be construed that such reference is prior art to the present application.